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20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis.
Int Immunopharmacol. 2018 Jun; 59:21-30.II

Abstract

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage.

Authors+Show Affiliations

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Intelligent Synthetic Biology Center, Daejeon 34141, Republic of Korea.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China. Electronic address: wangzi8020@126.com.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National& Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China. Electronic address: liwei7727@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29621733

Citation

Zhou, Yan-Dan, et al. "20(R)-ginsenoside Rg3, a Rare Saponin From Red Ginseng, Ameliorates Acetaminophen-induced Hepatotoxicity By Suppressing PI3K/AKT Pathway-mediated Inflammation and Apoptosis." International Immunopharmacology, vol. 59, 2018, pp. 21-30.
Zhou YD, Hou JG, Liu W, et al. 20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis. Int Immunopharmacol. 2018;59:21-30.
Zhou, Y. D., Hou, J. G., Liu, W., Ren, S., Wang, Y. P., Zhang, R., Chen, C., Wang, Z., & Li, W. (2018). 20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis. International Immunopharmacology, 59, 21-30. https://doi.org/10.1016/j.intimp.2018.03.030
Zhou YD, et al. 20(R)-ginsenoside Rg3, a Rare Saponin From Red Ginseng, Ameliorates Acetaminophen-induced Hepatotoxicity By Suppressing PI3K/AKT Pathway-mediated Inflammation and Apoptosis. Int Immunopharmacol. 2018;59:21-30. PubMed PMID: 29621733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis. AU - Zhou,Yan-Dan, AU - Hou,Jin-Gang, AU - Liu,Wei, AU - Ren,Shen, AU - Wang,Ying-Ping, AU - Zhang,Rui, AU - Chen,Chen, AU - Wang,Zi, AU - Li,Wei, Y1 - 2018/04/02/ PY - 2018/02/20/received PY - 2018/03/24/revised PY - 2018/03/28/accepted PY - 2018/4/6/pubmed PY - 2018/10/4/medline PY - 2018/4/6/entrez KW - 20(R)-ginsenoside-Rg3 KW - APAP-induced liver injury KW - Anti-apoptosis KW - Anti-inflammation KW - Oxidative stress KW - PI3K/AKT signaling pathway SP - 21 EP - 30 JF - International immunopharmacology JO - Int Immunopharmacol VL - 59 N2 - Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/29621733/20_R__ginsenoside_Rg3_a_rare_saponin_from_red_ginseng_ameliorates_acetaminophen_induced_hepatotoxicity_by_suppressing_PI3K/AKT_pathway_mediated_inflammation_and_apoptosis_ DB - PRIME DP - Unbound Medicine ER -